Stroke is the third leading cause of death in the United States and is considered to be the most common cause of adult disability. Pharmacological intervention has made little, if any, impact in preventing neurological damage that occurs during the hours and days following stroke onset. Reactive oxygen species (ROS) are strongly implicated in this damage. Eukarion has developed a series of low molecular weight synthetic compounds that are catalytic ROS scavengers, mimicking the antioxidants superoxide dismutase (SOD) and catalase, and are highly protective in rodent stroke models. This SBIR project will investigate the potential therapeutic value of these SOD/catalase mimics in stroke. During Phase I, several of the compounds were evaluated for their neuroprotective activity in the rodent stroke model, and for other relevant properties such as solubility and stability. Based on this research three compounds were selected as candidate molecules for preclinical and clinical development. Research proposed for Phase II will involve: (l) Safety screening studies to enable selection of one compound as the lead molecule ("EUK-n"); (2) Development of an injectable formulation for clinical administration of EUK-n; (3) Formal toxicity studies; and (4) Pharmacokinetic and biodistribution studies. This will provide necessary information to file an Investigational New Drug application with the FDA in order to initiate clinical trials with EUK-n. PROPOSED COMMERCIAL APPLICATION: Stroke affects about 500,000 patients annually in the U.S. and there is no satisfactory treatment to prevent the neurological darn age that results. Eukarion's novel SOD/catalase mimics are highly neuroprotective in rodent stroke models. This SBIR research will provide key preclinical information that will enable Eukarion to apply to the FDA for permission to initiate clinical trials with an SOD/catalase mimic.